The Th2 cytokine IL-10 inhibits hyaluronan mRNA accumulation in fibroblast-like synoviocytes
© The Author(s) 2003
Received: 14 January 2003
Published: 24 February 2003
IL-10 has been shown to be beneficial in a series of ailments, inflammatory arthritis among them.
In an attempt to study possible mechanisms we investigated the effect of IL-10 on mRNA accumulation of genes encoding hyaluronan. Hyaluronan and/or its degradation products have been implicated in the many detrimental effects associated with disease progression. Here we report that IL-10 suppresses noninduced as well as induced mRNA accumulation of certain genes encoding hyaluronan.
Human fibroblast-like synovial cells (FS) were studied for their potential to synthesize hyaluronan synthase (HAS) mRNA. Expression levels of mRNA for HAS1, HAS2 and HAS3 were monitored by RT-PCR. IL-10 was added to FS cultures for 6 hours.
HAS3 is constitutively expressed in FS. We found that treating FS with IL-10 inhibited HAS3 mRNA accumulation in a dose-dependent manner. Similar to HAS3, HAS2 mRNA was readily detectable in unstimulated FS. Our experiments show that in contrast to HAS3, IL-10 has no significant effect on HAS2 mRNA. Furthermore, in contrast to HAS3 and HAS2 mRNA levels in untreated FS, HAS1 mRNA is below or close to the detection limit in unstimulated FS but can be readily induced by stimulating these cells with TGF-β (1 ng/ml for 6 hours). We tested the potential of IL-10 to inhibit TGF-β-induced HAS1 mRNA synthase and found that IL-10 also inhibited TGF-β induced HAS1 mRNA, albeit to a lesser degree.
IL-10 can be a potent inhibitor of induced as well as non-induced HAS activation. While 10 ng/ml of IL-10 can reduce HAS3 levels in FS by more than 90%, the effect of IL-10 on TGF-β induced HAS1 levels is less pronounced. Taken together, it is tempting to speculate that the observed beneficial effects of IL-10 in rheumatoid arthritis are at least in part due to its inhibitory effect on HAS mRNA activation.